Effects of Testosterone on Brain Function on Elderly Men

睾酮对老年男性脑功能的影响

• 批准号: 6781451
• 负责人: SCOTT D. MOFFAT
• 金额: $ 6.8万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6781451
• 关键词: aging; clinical research; cognition; functional magnetic resonance imaging; hippocampus; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; male; memory; patient oriented research; performance; testosterone

This proposal is being submitted in response to NIA PAR 03-056. It is being submitted under the topic "Improve Quality of Life of Older People," guideline 11, Intervention Studies. In men, testosterone (T) levels decline by approximately 50% from ages 30 to 80 and a majority of men over age 70 can be classified as hypogonadal. This progressive loss of T with age in men, often called the "andropause", may have significant cognitive consequences. Indeed, among men with suspected andropause, memory loss is the third most commonly reported symptom. Both epidemiologic and intervention studies highlight the importance of T in maintaining cognitive function. Despite the high morbidity associated with T loss, there have been few studies specifically investigating the neurocognitive effects of T in elderly men. The long term goal of this program of research is to investigate the effects of steroid hormones on cognitive and brain aging. To that end, the specific objective is to investigate the effects of T on spatial memory and functional brain activation in hypogonadal men. Sixteen men will participate in a randomized, placebo-controlled, T intervention study. The principal outcome measures will be behavioral performance on virtual reality tests of spatial navigation and standardized tests of cognitive function. In addition, to assess the neural basis of T action, brain activation will be assessed by functional MRI during a virtual reality spatial memory task. Our central hypothesis is that T replacement will prove beneficial for neurocognitive function in elderly men. Specifically, we hypothesize that T supplementation will increase activation in the hippocampal and parahippocampal system supporting human spatial memory. This proposal is unique in its approach in that it adopts a virtual reality navigation task to assess cognitive and brain function in hypogonadal men. This task serves as an excellent neurocognitive probe to evaluate the hypotheses as it elicits brain activation and age-related changes in those specific neural systems that are demonstrably sensitive to T action. The proposed research is significant in that it will provide us with a detailed account not only of the cognitive systems modulated by T, but also provide us with a putative neural explanation of those same effects. Ultimately, this work will prove essential in the development of intervention strategies to prevent or ameliorate cognitive decline among at-risk elderly individuals.

本提案是根据NIA PAR 03-056提交的。它是在“改善老年人的生活质量”的指导方针11，干预研究下提交的。在男性中，从30岁到80岁，睾酮(T)水平下降了大约50%，70岁以上的大多数男性可以被归类为性腺功能低下。男性这种随年龄增长逐渐丧失T的现象，通常被称为“雄停滞”，可能会对认知产生重大影响。事实上，在疑似男性停滞症的男性中，记忆力丧失是第三种最常见的症状。流行病学和干预性研究都强调了T在维持认知功能方面的重要性。尽管与T丢失相关的发病率很高，但很少有研究专门研究T对老年男性的神经认知影响。这项研究的长期目标是调查类固醇激素对认知和大脑的影响。 衰老。为此，我们的具体目标是研究T对性腺功能减退男性的空间记忆和脑功能激活的影响。16名男性将参加一项随机、安慰剂对照的T干预研究。主要的结果衡量标准将是虚拟现实空间导航测试中的行为表现，以及认知功能的标准化测试。此外，为了评估T动作的神经基础，将在虚拟现实空间记忆任务中通过功能磁共振对大脑激活进行评估。我们的中心假设是，T替代疗法将证明对老年男性的神经认知功能有益。具体地说，我们假设补充T将增加支持人类空间记忆的海马体和副海马体系统的激活。这项建议的独特之处在于，它采用了一种虚拟现实导航任务来评估性腺功能低下的男性的认知和大脑功能。这项任务作为一个很好的神经认知探测器来评估这些假设，因为它引起了大脑激活和那些对T动作明显敏感的特定神经系统中与年龄相关的变化。这项研究具有重要意义，因为它不仅为我们提供了关于T调节认知系统的详细描述，而且还为我们提供了对这些相同影响的假设的神经解释。归根结底，这 在制定干预策略以预防或改善高危老年人的认知衰退方面，工作将被证明是必不可少的。